Sickle Cell DiseaseSCANCT05837871
Genetic and Haematological Modifiers of SCD Severity in Kaduna State, Northern Nigeria
An observational study of Sickle Cell Disease, run by Ahmadu Bello University Teaching Hospital.
Trial summary
This study is aimed to assess the genetic and haematological modifiers of disease severity among patients with Sickle Cell Disease (SCD) in Kaduna State, northern Nigeria. It is composed by two separate study designs: a cross-sectional study and a longitudinal study. Read more about this study
- Who is it for?
- Ages 9 months to 18 years
- Conditions the study is for
- Sickle Cell Disease
- How many people
- 400 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2023to 1 Jun 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Patients with Sickle Cell Anaemia attending Clinics in Ahmadu Bello University Teaching Hospital, Zaria Nigeria.
Who may be able to join
- (i) Paediatric patients (ages 2-18 years) with known HbSS genotype from case records. They will be recruited during routine visits at the haematology clinics.
- Patients in steady-state and in sickle cell crisis.
- Patients will be considered to be in steady-state if they are in a period free of crisis extending from at least three weeks since the last clinical event and three months or more since the last blood transfusion, to at least one week before the start of a new clinical event.
- Patients will be considered to be in sickle cell crisis (i.e. vaso-occlusive crisis, VOC) if they are known to have SCD, together with bone or joint pain, or multiple sites of pain, necessitating hospital admission and analgesic administration.
- Paediatric patients enrolled at 3 months of age with SCD diagnosed during newborn screening and followed over time at 6 months, 9 months, 12 months and 24 months of age.
- A written informed consent signed by all participants and/or parents/legally designated representatives is required to be recruited.
Who cannot join
- (i) Subjects with overt features of significant co-morbidities like malignancies, malnutrition, congenital deficiencies or severe infections.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Assessment of Genetic and Haematological Modifiers of Disease Severity Among Patients With Sickle Cell Disease (SCD) in Kaduna State, Northern Nigeria
This study is aimed to assess the genetic and haematological modifiers of disease severity among patients with Sickle Cell Disease (SCD) in Kaduna State, northern Nigeria. It is composed by two separate study designs: a cross-sectional study and a longitudinal study.
The cross-sectional study will evaluate clinical and laboratory parameters in paediatric Sickle Cell Anaemia (SCA) patients (ages 2-18 years) in steady state and during Vaso-Occlusive Crisis (VOCs) to determine the parameters that can be used as a guide to monitor the course of the disease towards early recognition and management of sickle cell crises. In addition, the study will explore genotype-phenotype correlations in SCA patients by targeted Next-Generation Sequencing (NGS) of genetic modifiers for haemoglobinopathies.
Read more
The longitudinal study will collect clinical and laboratory data over time for a paediatric cohort of SCD patients (9 months old; followed up to 2 years of age) and parental samples will be collected to determine the βS-globin haplotype in family trios. The aim is to determine the temporal relationships among foetal haemoglobin (HbF) levels, haematological parameters and frequency of sickle cell crises in SCD patients in relation to the type of the βS-globin haplotype and the sickle genotype. In addition, samples collected at 24 months of age will also be analysed by NGS to identify genetic modifiers of clinical manifestations and severity of SCA.
Participants from the following centre will be involved: Ahmadu Bello University Teaching Hospital (ABUTH) Zaria. Consent from all the study parents/legally designated representatives as well as assent from minors will be sought. Consent for genetic analyses will be sought as well. Clinical and haematological analyses will be performed at ABUTH while genetic analyses will be performed at the Cyprus Institute of Neurology and Genetics (CING).
Read the detailed description
Sickle cell anaemia (SCA) is a multisystem disorder with massive medical, social and financial implications worldwide. It is caused by a single mutation in the β-globin gene (β6 Glu>Val), which leads to the production of abnormal sickle haemoglobin (HbS). Africa is the major origin of the sickle (βS) mutation, which occurs on diverse genetic haplotype backgrounds. SCA has a Mendelian pattern of inheritance (βS gene homozygosity, i.e. HbSS). Although all SCA patients share the same genetic mutation, the disease exhibits wide heterogeneity in clinical expression, which can be explained by both environmental and genetic factors. The environmental factors include infections, trauma, climate (temperature and humidity) and air quality, as well as socioeconomic factors, many of which are controllable. The genetic factors, on the other hand, cannot be controlled. The best-characterized genetic factors include variants in the genes associated with foetal haemoglobin (HbF) production, co-inheritance of alpha-thalassaemia, sickle genotype, and the type of βS-globin haplotype. The role of other potential genetic modifiers is less clear, particularly with regards to sickle cell disease related organ damage (e.g., risk for stroke, haemolysis, and acute chest syndrome.
Understanding the molecular basis of clinical heterogeneity and disease severity for SCA can have direct clinical applications for prognosis via risk stratification of patients, also facilitating the use of personalized, targeted therapeutic interventions. As a turning-point in genomics, the advent of high-throughput sequencing and whole-genome analysis has made it feasible to discover hitherto unsuspected variants that could add to current understanding of genotype-phenotype relationships in SCA. The identification of modifying genetic variants might suggest new prognostic and/or therapeutic targets for investigation towards improved patient management and treatment.
- Conditions
- Sickle Cell Disease
- Keywords
- Genetics, Haematological parameters, Modifiers, Sickle Cell Disease, Kaduna, Nigeria, Assessment
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cross sectional arm | Patients with Sickle Cell Anaemia aged 2 to 18 years. Assessed for clinical severity, Complete Blood Count, foetal haemoglobin and Haemoglobin Haplotype | |
| Longitudinal arm | * Patients with Sickle Cell Anaemia recruited at 9 months of age then followed up at 12 months, 18 months and 24 months. * Assessed for clinical severity, Complete Blood Count, foetal haemoglobin and Haemoglobin Haplotype * Both parents assesed for Haemoglobin Haplotype * Genotype - Haplotype assessment to be carried out |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cross sectional arm
Subjects with Sickle Cell disease (n=200), aged 2 - 18 years will be recruited for this arm of the study
- Clinical severity using the severity index developed by van den Tweel et al in PMID 20806231
- Complete blood count using Coulter Haematology Auto-analyzer: WBC (10^9/L), RBC (10^12/L), Hb (g/L), HCT (%), PLT (10^9/L), MCV (fl), MCH (pg), MCHC (g/L)
- Foetal haemoglobin using HPLC - 10 machine: (%)
- Hemoglobin haplotype using a SNPs test [RFLP-PCR] to determine beta S-globin haplotypes
Measured: 3 months
Secondary outcomes (1)
Longitudinal arm
Subjects with SCD (n=200) at 9 months of age will be recruited and followed up at 12months, 18months and 24months
- Clinical severity index developed by van den Tweel et al in PMID 20806231, will be assessed at each follow-up contact.
- Complete blood count using Coulter Haematology Auto-analyzer: WBC (10^9/L), RBC (10^12/L), Hb (g/L), HCT (%), PLT (10^9/L)
- Foetal haemoglobin using HPLC - 10 machine: (%)
- Hemoglobin analysis using a SNPs test [RFLP-PCR] to determine beta S-globin haplotype.
- Spatial relationship of parameters (Blood counts, Severity scores, Level of HbF) will be correlated (using Spearman or Pearson), depending on normality of distribution of the data.
- Parental samples (of each subject above) will be obtained for genomic characterization of Beta S globin gene in family trios.
- Chi-squrared test or Wilcoxon's (as appropriate) will be used to associate certain outcome measures (e.g., HbF, severity) with specific beta S globin gene haplotypes
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2023
- Study start1 May 2023 (estimated)
- Primary completion1 May 2025 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ahmadu Bello University Teaching Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Cyprus Institute of Neurology and Genetics
- Responsible party
- Principal investigator, Bello Jamoh Yusuf, Ahmadu Bello University Teaching Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05837871
- Sponsor's protocol ID
- ABUTH
- Acronym
- SCA
- Status last verified
- Apr 2023
- First submitted
- 14 Mar 2023
- Last updated
- 1 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be freely shared with researchers and students
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Genetic and Haematological Modifiers of Disease Severity Among Patients With Sickle Cell Disease (SCD) in Kaduna State, Northern Nigeria
- ClinicalTrials.gov ID
- NCT05837871
- Acronym / sponsor ID
- SCA / ABUTH
- Conditions
- Sickle Cell Disease
- Keywords
- Genetics, Haematological parameters, Modifiers, Sickle Cell Disease, Kaduna, Nigeria, Assessment
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Ahmadu Bello University Teaching HospitalUniversity, hospital or other
- Collaborators
- Cyprus Institute of Neurology and Genetics
- Study start
- 1 May 2023 (estimated)
- Primary completion
- 1 May 2025 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 1 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is aimed to assess the genetic and haematological modifiers of disease severity among patients with Sickle Cell Disease (SCD) in Kaduna State, northern Nigeria. It is composed by two separate study designs: a cross-sectional study and a longitudinal study.
The cross-sectional study will evaluate clinical and laboratory parameters in paediatric Sickle Cell Anaemia (SCA) patients (ages 2-18 years) in steady state and during Vaso-Occlusive Crisis (VOCs) to determine the parameters that can be used as a guide to monitor the course of the disease towards early recognition and management of sickle cell crises. In addition, the study will explore genotype-phenotype correlations in SCA patients by targeted Next-Generation Sequencing (NGS) of genetic modifiers for haemoglobinopathies.
The longitudinal study will collect clinical and laboratory data over time for a paediatric cohort of SCD patients (9 months old; followed up to 2 years of age) and parental samples will be collected to determine the βS-globin haplotype in family trios. The aim is to determine the temporal relationships among foetal haemoglobin (HbF) levels, haematological parameters and frequency of sickle cell crises in SCD patients in relation to the type of the βS-globin haplotype and the sickle genotype. In addition, samples collected at 24 months of age will also be analysed by NGS to identify genetic modifiers of clinical manifestations and severity of SCA.
Participants from the following centre will be involved: Ahmadu Bello University Teaching Hospital (ABUTH) Zaria. Consent from all the study parents/legally designated representatives as well as assent from minors will be sought. Consent for genetic analyses will be sought as well. Clinical and haematological analyses will be performed at ABUTH while genetic analyses will be performed at the Cyprus Institute of Neurology and Genetics (CING).
Detailed description
Sickle cell anaemia (SCA) is a multisystem disorder with massive medical, social and financial implications worldwide. It is caused by a single mutation in the β-globin gene (β6 Glu>Val), which leads to the production of abnormal sickle haemoglobin (HbS). Africa is the major origin of the sickle (βS) mutation, which occurs on diverse genetic haplotype backgrounds. SCA has a Mendelian pattern of inheritance (βS gene homozygosity, i.e. HbSS). Although all SCA patients share the same genetic mutation, the disease exhibits wide heterogeneity in clinical expression, which can be explained by both environmental and genetic factors. The environmental factors include infections, trauma, climate (temperature and humidity) and air quality, as well as socioeconomic factors, many of which are controllable. The genetic factors, on the other hand, cannot be controlled. The best-characterized genetic factors include variants in the genes associated with foetal haemoglobin (HbF) production, co-inheritance of alpha-thalassaemia, sickle genotype, and the type of βS-globin haplotype. The role of other potential genetic modifiers is less clear, particularly with regards to sickle cell disease related organ damage (e.g., risk for stroke, haemolysis, and acute chest syndrome.
Understanding the molecular basis of clinical heterogeneity and disease severity for SCA can have direct clinical applications for prognosis via risk stratification of patients, also facilitating the use of personalized, targeted therapeutic interventions. As a turning-point in genomics, the advent of high-throughput sequencing and whole-genome analysis has made it feasible to discover hitherto unsuspected variants that could add to current understanding of genotype-phenotype relationships in SCA. The identification of modifying genetic variants might suggest new prognostic and/or therapeutic targets for investigation towards improved patient management and treatment.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cross sectional arm | – | –Patients with Sickle Cell Anaemia aged 2 to 18 years. Assessed for clinical severity, Complete Blood Count, foetal haemoglobin and Haemoglobin Haplotype |
| Longitudinal arm | – | –* Patients with Sickle Cell Anaemia recruited at 9 months of age then followed up at 12 months, 18 months and 24 months. * Assessed for clinical severity, Complete Blood Count, foetal haemoglobin and Haemoglobin Haplotype * Both parents assesed for Haemoglobin Haplotype * Genotype - Haplotype assessment to be carried out |
Who may qualify
- Ages
- 9 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Patients with Sickle Cell Anaemia attending Clinics in Ahmadu Bello University Teaching Hospital, Zaria Nigeria.
Key inclusion criteria (6 listed)
- (i) Paediatric patients (ages 2-18 years) with known HbSS genotype from case records. They will be recruited during routine visits at the haematology clinics.
- Patients in steady-state and in sickle cell crisis.
- Patients will be considered to be in steady-state if they are in a period free of crisis extending from at least three weeks since the last clinical event and three months or more since the last blood transfusion, to at least one week before the start of a new clinical event.
- Patients will be considered to be in sickle cell crisis (i.e. vaso-occlusive crisis, VOC) if they are known to have SCD, together with bone or joint pain, or multiple sites of pain, necessitating hospital admission and analgesic administration.
- Paediatric patients enrolled at 3 months of age with SCD diagnosed during newborn screening and followed over time at 6 months, 9 months, 12 months and 24 months of age.
Key exclusion criteria (1 listed)
- (i) Subjects with overt features of significant co-morbidities like malignancies, malnutrition, congenital deficiencies or severe infections.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Cross sectional arm
Time frame: 3 months
Subjects with Sickle Cell disease (n=200), aged 2 - 18 years will be recruited for this arm of the study * Clinical severity using the severity index developed by van den Tweel et al in PMID 20806231 * Complete blood count using Coulter Haematology Auto-analyzer: WBC (10^9/L), RBC (10^12/L), Hb (g/L), HCT (%), PLT (10^9/L), MCV (fl), MCH (pg), MCHC (g/L) * Foetal haemoglobin using HPLC - 10 machine: (%) * Hemoglobin haplotype using a SNPs test [RFLP-PCR] to determine beta S-globin haplotypes
1 secondary outcome
Longitudinal arm
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2023.
- Individual participant dataSharing planned: Yes. IPD will be freely shared with researchers and students
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease, run by Ahmadu Bello University Teaching Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 May 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bello Jamoh Yusuf, Dr (08033733152 ext. +234, bjamoh@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cross sectional arm (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2023.